This research project will determine whether the increased proteolytic enzyme activity which has been observed in virus transformed cells is responsible for several structural and functional changes previously detected in the plasma membrane of transformed cells. By blocking the proteolytic enzyme activity with nontoxic protease inhibitors, we will determine whether the increased protease activity is responsible for the cell surface changes and, most importantly, whether the cell surface changes are responsible for the loss of density-dependent growth inhibition characteristic of virus-transformed cells. In addition, we propose to isolate and characterize a factor, found in increased amounts in the medium of SV3T3 cells compared with 3T3 cells, which causes inhibition of guinea pig macrophage migration in vitro. This factor may be a proteolytic enzyme and may be responsible for the previously observed loss of a dense-staining cell surface material from SV3T3 and inhibited macrophage cell surfaces.